姓名 | 朱雯雯 蒋鑫 吴沛
Unit | Jinshan Hospital Affiliated to Fudan University
Foreword
Monoclonal immunoglobulin (Monoclonal Protein or Myeloma Protein, M protein), also known as paraprotein, is mainly secreted by a large number of plasma cells with abnormal clonal hyperplasia, and its essence is an immunoglobulin (Ig), which is more common in monoclonal immunoglobulin proliferative diseases, such as: multiple myeloma (MM), Waldenstrom macroglobulinemia (VM), plasmacytoma, Primary amyloidosis and monoclonal γ globulinemia of undetermined significance (MGUS), among others[1]. At present, there have been several articles reported on the interference of M protein in the detection of clinical biochemical projects [2]. However, the effect of M protein on coagulation appears to be limited, and this case will describe a case of M protein affecting coagulation assays.
Case History
The patient, a 79-year-old male, was admitted to the emergency department with intracranial hemorrhage and a history of hypertension. After receiving the sample, the emergency personnel centrifuged the machine, and the coagulation function was as follows: PT: 12.57s, FIB: 1.69g/L, APTT: 65.42s, TT: 17.92s, AT: 57%, FDP: 7.60 μg/mL, D-D: 0.54 μg/mL.
During the audit report, it was found that the D-D dimer had an "*" prompt, and interference was suspected. Immediately check the instrument prompt "lipid blood interference is too strong". However, the plasma appearance of the sample was clear, no lipidemia, hemolysis, and jaundice, and the patient's biochemical report was reviewed, and the TG, CHOL, TB, BU, BC were all within the normal range, and there was no previous history of hyperlipidemia.
What is the reason for the instrument to alarm the lipid-free blood sample with "suspected lipid interference"?
Consult the manufacturer's engineer instrument alarm logic, the coagulation instrument uses the colorimetric cell method to detect the HIL grade of the sample (H: hemolysis, I: jaundice, L: lipid blood) The specific detection steps are: absorb 16uL sample and 200uL dilution to the colorimetric cell, and then detect the absorbance of the diluted sample through the three-color LED, calibrate and convert the concentration of H (hemolysis), I (jaundice), L (lipid blood), and divide the grade.
The consulting team leader believes that it may be a "lipid-like blood sample change" produced after the sample is diluted, which causes the instrument to alarm "lipid interference". Therefore, the plasma was diluted 20 times with pure water, and it was found that the sample did become turbid. Subsequently, the sample was sent to the biochemistry laboratory for serum protein electrophoresis, and the suspicious M protein was found. This information is provided to the clinic, and the clinician prescribes serum protein electrophoresis and immunofixation electrophoresis, and finally, the patient's monoclonal immunoglobulin type is determined to be IgM-κ.
Case Study
Common factors that interfere with detection include hemolysis, jaundice, lipidemia, etc., and the interference of specimen components is easy to ignore. In recent years, there have been many papers at home and abroad that have reported the effect of M protein on biochemical detection, and the precipitation of M protein under specific conditions can interfere with colorimetric and turbidity analysis, or cause false results to interfere with detection results due to specific or non-specific binding with components in the analytical system [3].
High concentrations of M protein have been reported to cause falsely high or falsely low values in serum creatinine, uric acid, lipoprotein, total protein, bilirubin, blood glucose, blood phosphate, hemoglobin, and glycosylated albumin, and abnormal presence of M protein in 25‐OH vitamin D, thyroid-stimulating hormone, C-reactive protein, vancomycin, gentamicin, and sodium valproate has interfered with actual results [4].
In the clinical laboratory, M protein interference has not attracted enough attention from experimenters, and in the process of testing, the detector finds that the instrument prompt is inconsistent with the specimen status or the test results are inconsistent with the actual situation of the patient.
For interference with M protein, dilution of patient serum or protein removal, use of protein stabilizers, or optimization of reaction conditions can be used. Low levels of M protein can be diluted with deionized water, generally speaking, the patient's serum (original times) is clear and transparent, the original times of the specimen by deionized water diluted 5, 10, 20 times, the obtained specimen is obviously turbid, it has been reported that the high immunoglobulin sample when diluted with pure water, will reduce the ionic strength in the sample, resulting in the cross-linking aggregation of high immunoglobulin resulting in turbidity.
In the clinical laboratory, the most common analytical methods are colorimetric analysis and turbidity analysis, biochemistry and hemagglutination detection are mostly used in these two methods, if the sample contains M protein, the results will be biased, we can find the occult M protein through the instrument prompt and patient test results, to provide clinicians with more comprehensive detection information.
Summary
In daily work, in addition to the need to pay attention to the interference factors such as hemolysis, lipid blood and jaundice, the inspection workers must pay full attention to the interference of M protein, which may be positive interference or negative interference. At present, clinical laboratories have not set up special tests for M protein interference, and it is suggested that clinical laboratories should formulate corresponding testing standards according to clinical needs and testing capabilities, and establish effective examination methods to detect M protein interference.
bibliography
[1] Zhang Yiru, Liu Feng, Tian Hong, et al.Clinical significance of M protein concentration detection in patients with monoclonal immunoglobulinemia[J].Journal of Nephrology and Dialysis Kidney Transplantation,2021,30(2):130-135.
[2] Zhou Xiaona, Fang Honggang, Cao Yanfei, et al.Interference analysis in the detection of serum uric acid by uricase-peroxidase coupling reaction[J].Diagnostics - Theory & Practice,2020,19(4):426-429.
[3] YANG Y,HOWANITZ P J,HOWANITZ J H,et al. Paraproteins are a common cause of interferences with auto mated chemistry methods[J]. Arch Pathol Lab Med,2008,132(2):217-223.
[4] Pan Xiaoyuan, et al. Research Progress of M Protein Interfering with Clinical Laboratory Detection Projects.Diagnostics Theory & Practice.22.04(2023).
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